Andy V. Babwah
Associate Professor
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PH.D. McGill University |
The overall goal of my research program is to understand the roles of the gonadotropin releasing hormone receptor (GnRH-R) in the pre-implantation period of mammalian development and placentation and to determine the effects of dysregulated receptor activity on these important processes. GnRH is a key regulator of the reproductive hormone cascade. Humans express two forms of this decapeptide hormone, GnRH-I and GnRH-II and their effects are mediated by GnRH-RI, a heptahelical G protein-coupled receptor (GPCR). To date, only one functional form of this receptor has been identified in man and, like its cognate ligands, it is expressed in multiple cell-types throughout the body with a single cell-type often expressing the receptor and its ligands. These cells include the anterior pituitary gonadotropes and placental cytotrophoblasts. The pre-implantation period of mammalian development is essential for reproductive success. This period of development is initiated by fertilization of the egg by sperm and terminates with implantation of the embryo into the uterine wall. In humans, early pregnancy loss, pre-term delivery and infertility are all due in part to diminished pre-implantation embryo health. Placentation refers to the growth and formation of the placenta and the development of the uterine capacity to supply the blood required by the fetus. During the first trimester of human pregnancy, maternal spiral arteries of the uterus are remodeled resulting in a high-flow, low-resistance circulation that increases maternal blood flow to the placental villi at the maternal-fetal interface. Impaired remodeling of the maternal spiral arteries is believed to be a major contributing factor to pre-eclampsia (PE). PE is the second most common cause of maternal mortality, and with over 100,000 deaths/year worldwide, it is associated with fetal growth restriction due to utero-placental insufficiency. Despite improvements in diagnosis and treatment, these disorders are still associated with significant maternal morbidity and mortality, primarily because of hemorrhage. A better understanding of the role of GnRH-R signaling during pre-implantation embryo development and placentation is therefore required. The knowledge derived from these studies will increase our ability to develop treatments to enhance human embryo health and development, embryo attachment to the uterine wall and placenta development, thereby increasing the chances of healthy pregnancy.
Holmes K, Babwah AV et al. (2006). Differential regulation of corticotrophin releasing factor 1α receptor endocytosis and trafficking by β-arrestins and RAB GTPases. Journal of Neurochemistry 96:934-949. Dhami GK, Babwah AV et al. (2005). Phosphorylation-independent Regulation of Metabotropic Glutamate Receptor 1 Signaling Requires G Protein-coupled Receptor Kinase 2 Binding to the Second Intracellular Loop. Journal of Biological Chemistry 280: 24420-24427. Bhattacharya M, Babwah AV, Ferguson SSG (2004). Small GTP-binding protein-coupled receptors (Review). Biochemical Society Transactions 32:1040-1044. Bhattacharya M, Babwah AV (co-first author) et al. (2004). Ral and phospholipase D2-dependent pathway for constitutive metabotropic glutamate receptor endocytosis. The Journal of Neuroscience 24:8752-8761. Babwah AV et al. (2003). Protein kinase C isoform-specific differences in the spatial-temporal regulation and decoding of metabotropic glutamate receptor 1a-stimulated second messenger responses. Journal of Biological Chemistry 278: 5419-5426.
